Project Summary: The overall goals of the Structural Biology (SB) core are to apply structural techniques to the analysis of important biological macromolecules and their signaling networks, to provide basic knowledge of disease mechanisms, drive research and direct the synthesis of novel therapeutics. When diffraction quality crystals can be grown then atomic images of the arrangement of amino acid side chains in three dimensions can be obtained. These images give the atomic detail needed to visualize the active sites of enzymes, see the DNA binding sites of transcription factors and view the protein-protein interactions of signaling molecules. Function can be understood through determination of atomic structures. In the absence of crystals, the molecular envelopes of macromolecular complexes, individual proteins and their gross conformational changes upon ligand binding can be determined using small angle X-ray scattering (SAXS). Posttranslational modifications (PTMs) alter protein structure and are important for cell signaling. PTMs can be studied using western analysis and isoelectric focusing (IEF). The SB core provides nanocapillary electrophoresis (nanoELP) immunoassays for the characterization of PTMs. When combined these data allow researchers to learn how to modify the structure/function relationships of macromolecules; a key component to developing specific therapies without side effects.